Total submissions: 29
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Evidence- |
RCV000112415 | SCV000244371 | benign | Breast-ovarian cancer, familial, susceptibility to, 1 | 2015-08-10 | reviewed by expert panel | curation | IARC class based on posterior probability from multifactorial likelihood analysis, thresholds for class as per Plon et al. 2008 (PMID: 18951446). Class 1 based on posterior probability = 0.00000495. Also class 1 based on frequency >1% in an outbred sampleset. Frequency 0.01399 (Asian), derived from 1000 genomes (2012-04-30). |
Invitae | RCV001084481 | SCV000076696 | benign | Hereditary breast ovarian cancer syndrome | 2024-02-01 | criteria provided, single submitter | clinical testing | |
Counsyl | RCV000112415 | SCV000154024 | likely benign | Breast-ovarian cancer, familial, susceptibility to, 1 | 2014-03-07 | criteria provided, single submitter | literature only | |
Ambry Genetics | RCV000162565 | SCV000212978 | benign | Hereditary cancer-predisposing syndrome | 2014-11-18 | criteria provided, single submitter | clinical testing | This alteration is classified as benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |
CHEO Genetics Diagnostic Laboratory, |
RCV000120263 | SCV000219252 | benign | not specified | 2016-12-29 | criteria provided, single submitter | clinical testing | |
Michigan Medical Genetics Laboratories, |
RCV000112415 | SCV000267716 | benign | Breast-ovarian cancer, familial, susceptibility to, 1 | 2016-04-21 | criteria provided, single submitter | clinical testing | |
Laboratory for Molecular Medicine, |
RCV000120263 | SCV000538434 | likely benign | not specified | 2016-03-29 | criteria provided, single submitter | clinical testing | Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: ExAC: 0.8% (51/6614) Finnish; ClinVar: 6 B/LB |
Color Diagnostics, |
RCV000162565 | SCV000683224 | benign | Hereditary cancer-predisposing syndrome | 2014-12-30 | criteria provided, single submitter | clinical testing | |
Genome Diagnostics Laboratory, |
RCV000112415 | SCV000743386 | benign | Breast-ovarian cancer, familial, susceptibility to, 1 | 2017-07-28 | criteria provided, single submitter | clinical testing | |
Clinical Genetics DNA and cytogenetics Diagnostics Lab, |
RCV000112415 | SCV000744606 | benign | Breast-ovarian cancer, familial, susceptibility to, 1 | 2015-09-21 | criteria provided, single submitter | clinical testing | |
Preventiongenetics, |
RCV000034754 | SCV000806963 | likely benign | not provided | 2017-08-03 | criteria provided, single submitter | clinical testing | |
Mendelics | RCV000112415 | SCV001140506 | benign | Breast-ovarian cancer, familial, susceptibility to, 1 | 2019-05-28 | criteria provided, single submitter | clinical testing | |
Illumina Laboratory Services, |
RCV000112415 | SCV001287202 | benign | Breast-ovarian cancer, familial, susceptibility to, 1 | 2017-04-27 | criteria provided, single submitter | clinical testing | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign. |
ARUP Laboratories, |
RCV000034754 | SCV001473746 | benign | not provided | 2020-03-12 | criteria provided, single submitter | clinical testing | |
Ce |
RCV000034754 | SCV002063617 | likely benign | not provided | 2023-11-01 | criteria provided, single submitter | clinical testing | BRCA1: BP4, BS2 |
Genetic Services Laboratory, |
RCV000120263 | SCV002065609 | benign | not specified | 2021-11-22 | criteria provided, single submitter | clinical testing | |
National Health Laboratory Service, |
RCV001084481 | SCV002504994 | benign | Hereditary breast ovarian cancer syndrome | 2022-04-19 | criteria provided, single submitter | clinical testing | |
Sema4, |
RCV000162565 | SCV002537794 | benign | Hereditary cancer-predisposing syndrome | 2020-10-16 | criteria provided, single submitter | curation | |
Center for Genomic Medicine, |
RCV000120263 | SCV002550962 | benign | not specified | 2023-08-15 | criteria provided, single submitter | clinical testing | |
Fulgent Genetics, |
RCV002496524 | SCV002813733 | likely benign | Familial cancer of breast; Breast-ovarian cancer, familial, susceptibility to, 1; Pancreatic cancer, susceptibility to, 4; Fanconi anemia, complementation group S | 2022-05-24 | criteria provided, single submitter | clinical testing | |
Biesecker Lab/Clinical Genomics Section, |
RCV000034754 | SCV000043155 | probably not pathogenic | not provided | 2012-07-13 | no assertion criteria provided | research | Converted during submission to Likely benign. |
ITMI | RCV000120263 | SCV000084415 | not provided | not specified | 2013-09-19 | no assertion provided | reference population | |
Breast Cancer Information Core |
RCV000112415 | SCV000145201 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 1 | 2002-05-29 | no assertion criteria provided | clinical testing | |
CSER _CC_NCGL, |
RCV000148381 | SCV000190079 | likely benign | Breast neoplasm | 2014-06-01 | no assertion criteria provided | research | |
Department of Pathology and Laboratory Medicine, |
RCV001353702 | SCV000591545 | benign | Malignant tumor of breast | no assertion criteria provided | clinical testing | The BRCA1 p.Met1628Thr variant was identified in at least 105 of 111464 proband chromosomes (frequency: 0.001) from individuals or families with breast or ovarian cancer, and was present in 55 of 1140 control chromosomes (frequency: 0.048) (Inoue 1995, Judkins 2005, Ostrow 2004, Phelan 2004, Tavtigian 2006, Tamboom 2010). The variant was listed in dbSNP (ID: rs4986854) “With untested allele”, with a minor allele frequency of 0.004 (1000 Genomes Project); in HapMap-JPT cohort with a frequency of 0.041, and the PAC1 cohort with a frequency of 0.21; and Inoue (1995) found the variant allele at a frequency of 0.39 in a Japanese group of healthy control individuals. The identification of the variant in these population cohorts increases the likelihood that this is a low frequency benign variant in certain populations of origin. The variant was also identified in HGMD, LOVD, the BIC database (96X with unknown clinical importance), and UMD (4X as a neutral variant). In UMD the variant was identified with a co-occurring pathogenic BRCA2 variant (c.4576dup (p.Thr1526AsnfsX3)), and Judkins (2005) observed the variant in trans with three different pathogenic BRCA1 mutations, increasing the likelihood that the p.Met1628Thr variant does not have clinical significance. In addition, a study by Phelan (2004) found that the variant did not segregate with disease in one family, and two functional studies showed no showed no effect of the variant on transcriptional activation (Phelan 2004, Ostrow 2004). Furthermore, Myriad classifies this variant as a polymorphism (personal communication). In summary, based on the above information, this variant meets our laboratory's criteria to be classified as benign. | |
True Health Diagnostics | RCV000162565 | SCV000787906 | likely benign | Hereditary cancer-predisposing syndrome | 2017-12-01 | no assertion criteria provided | clinical testing | |
Clinical Genetics Laboratory, |
RCV000120263 | SCV001905755 | benign | not specified | no assertion criteria provided | clinical testing | ||
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, |
RCV000120263 | SCV001951815 | benign | not specified | no assertion criteria provided | clinical testing | ||
BRCAlab, |
RCV000112415 | SCV004243969 | benign | Breast-ovarian cancer, familial, susceptibility to, 1 | 2020-03-02 | no assertion criteria provided | clinical testing |